Does plozasiran reduce the risk of recurrent pancreatitis in severe hypertriglyceridemia?

Severe hypertriglyceridemia (very high blood triglycerides) can lead to acute pancreatitis, a painful and dangerous inflammation of the pancreas. Plozasiran is a new medication that lowers triglycerides by blocking a protein called apolipoprotein C-III. A recent analysis of a clinical trial found that plozasiran significantly reduces the chance of having another pancreatitis attack in people who have already had one.

What the research says

A post hoc analysis of the PALISADE trial looked at 67 people with severe hypertriglyceridemia (median triglycerides over 2000 mg/dL) and a history of pancreatitis ⁴⁶. Participants received either plozasiran (25 or 50 mg) or a placebo injection every three months for one year ⁴⁶. Plozasiran lowered triglycerides by more than 75%, bringing median levels below 500 mg/dL ⁴⁶. Over the study, acute pancreatitis occurred in 5 of 22 people in the placebo group but only 2 of 45 in the plozasiran group ⁴⁶. This represents an 83% reduction in the risk of recurrent pancreatitis (hazard ratio 0.17, p<0.017) ⁴⁶. Plozasiran also reduced hospitalizations for abdominal pain and the length of hospital stays ⁴. Other drugs in the same class, such as olezarsen and volanesorsen, also lower triglycerides by 40–70% and reduce pancreatitis risk, but plozasiran is the first to show this specific effect in a dedicated analysis ³⁷. The PALISADE trial was double-blind and placebo-controlled, but the pancreatitis analysis was post hoc, meaning it was not the main planned analysis ⁴⁶.

What to ask your doctor

• Could plozasiran be an option for me given my history of pancreatitis?
• What are the potential side effects of plozasiran, and how does it compare to other triglyceride-lowering medications?
• Do I need to continue lifestyle changes like a low-fat diet and exercise while on plozasiran?
• How often would I need injections, and what monitoring is required during treatment?